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Science 307 (5706): 117-121

Copyright © 2005 by the American Association for the Advancement of Science

Requirement of Voltage-Gated Calcium Channel ß4 Subunit for T Lymphocyte Functions

Abdallah Badou,1 Srisaila Basavappa,2,4 Rooma Desai,3 You-Qing Peng,4 Didi Matza,1 Wajahat Z. Mehal,1 Leonard K. Kaczmarek,2,3 Emile L. Boulpaep,2 Richard A. Flavell1*

Abstract: Calcium is known to play vital roles in diverse physiological processes, and it is known that voltage-gated calcium channels (Cav) mediate calcium influx in excitable cells. However, no consensus exists on the molecular identity of the calcium channels present in nonexcitable cells such as T lymphocytes. Here, we demonstrate that T lymphocytes express both regulatory ß4 and poreforming Cav1 {alpha}1 subunits of Cav channels. Cav ß4-mutant T lymphocytes fail to acquire normal functions and display impairment in the calcium response, activation of the transcription factor NFAT, and cytokine production. Although Cav1 channels of lymphocytes retain their voltage dependency, T cell receptor stimulation dramatically increases channel opening, providing a new mechanism for calcium entry in lymphocytes.

1 Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
2 Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA.
3 Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.
4 Digestive Diseases Unit, Department of Medicine, Pharmacology and Physiology, University of Rochester School of Medicine.

* To whom correspondence should be addressed. E-mail: richard.flavell{at}yale.edu


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